Application of ultrasound elastography for monitoring the effects of T[beta]R1 shRNA therapy on hepatic fibrosis in a rat model

• Published in: PloS one 2021-06, Vol.16 (6), p.e0253150
• Main Authors: Shi, Xiangzhou, Li, Jinghua, Min, Binying, Yang, Ruijing, He, Chunxiang, Yang, Yilin
• Format: Article
• Language: English
• Subjects: Diagnosis; Evaluation; Fibrosis; Liver diseases; Ultrasound imaging
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0253150

To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-[beta]1 signaling pathway-targeted combination therapy for hepatic fibrosis. 1. Short hairpin RNA (shRNA) constructs targeted towards T[beta]R1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. 1. An shRNA interference sequence targeted towards T[beta]R1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups af